Blondet_1997_J.Neurol.Sci_153_20

Several new neurotrophic factors have been recently identified and shown to prevent motoneuron death in vitro and in vivo. One such agent is brain-derived neurotrophic factor (BDNF). In this study, we tested BDNF on an animal model of early-onset motoneuron disease: the paralyse mouse mutant, characterized by a progressive skeletal muscle atrophy and the loss of 30-35% of spinal lumbar motoneurons between the first and second week post-natal. The results show that subcutaneous injections of 1 or 10 mg/kg BDNF did not have any significant effect in increasing the mean survival time of mutant mice or in preventing the loss of motor function and total body weight in paralyse mice. The weight and choline acetyltransferase activity of specific muscles and the number of motoneurons in the spinal cords were identical in BDNF-treated and placebo-injected paralyse mice. These results suggest that BDNF does not act on the disease process in paralyse mice in the conditions we used. By contrast, BDNF has previously been shown to partially prevent the loss of motor function in the wobbler mouse, a suggested model of later-onset motoneuron disease. Taken together these findings suggest that BDNF acts differently on early and late-onset motoneuron diseases. It is however possible that treatment of paralyse mice with BDNF or combinations of different neurotrophic factors prior to the phenotypical expression of the paralyse mutation may prevent the loss of motor function and motoneurons in mutant mice.